Case Management of Suspect Avian Influenza A H5N1 Virus Infection in Humans

1
Case Management of Suspect Avian Influenza A
(H5N1) Virus Infection in Humans

• Part 1 Background information on clinical
  features of human infection with avian influenza
  A (H5N1) viruses

May, 2007
2
Learning Objectives

• Recognize clinical features of avian Influenza A
  (H5N1) virus infection in humans
• Understand how information about the patient
  before onset of illness can help you suspect H5N1
  virus infection

3
Part 1 Session Outline

• Clinical features
• Epidemiological Context
• Exposure

4
Illness Scenario

• Alex sick for three days
• Fever
• Headache
• Cough
• Shortness of breath
• Muscle aches
• Watery diarrhea
• No one else sick
• Works at poultry farm and handles poultry
• Question Is avian Influenza A (H5N1) the most
  likely cause of Alexs symptoms?

5
Clinical Features
6
General Information
7
Signs and Symptoms
8
Laboratory Findings

• Commonly associated with human infection with
  avian influenza A (H5N1) viruses
• Drop in white blood cell count (leukopenia)
• Drop in lymphocytes, a kind of white blood cells
  (lymphopenia)
• Mild to moderate drop in blood platelet count
• Increased aminotransferases (liver enzymes)

9
Unusual Clinical Manifestations and Outcomes

• Knowledge of avian influenza A (H5N1) virus
  infection in humans is still evolving
• Unusual symptoms
• Southern Vietnam encephalitis and diarrhea
• Fever and diarrhea can be the only early signs
  and symptoms before pneumonia occurs later with
  H5N1 virus infection

10
Complications

• H5N1 Virus Infection in Humans
• Most cases develop pneumonia
• Acute Respiratory Distress Syndrome (ARDS)
• Multiorgan failure
• Encephalitis
• Cytokine storm

• Seasonal Influenza
• Ear infections, sinusitis
• Bronchitis, bronchiolitis
• Pneumonia
• viral or secondary bacterial
• Exacerbation of chronic conditions
• Muscle inflammation
• Neurologic Disease
• Seizures
• Encephalopathy and encephalitis
• Reye syndrome

11
Alex

• Question
• Do you think Alex has signs and symptoms of
  H5N1? Why or why not?

12
Epidemiological Context
13
Exposure to Avian Influenza (H5N1) Virus

• Infected poultry, particularly coming in contact
  with respiratory secretions
• Infected wild or pet birds
• Other infected animals (e.g., pigs, cats, dogs)
• Wild bird feces, poultry manure and litter
  containing high concentrations of virus
• Fecally contaminated surfaces

14
H5N1 Virus Exposures Continued

• Under- or uncooked poultry meat or eggs from
  infected birds
• Contaminated vehicles, equipment, clothing, and
  footwear at affected sites, such as poultry farms
  with outbreaks
• Contaminated air space (e.g., a barn, hen-house,
  or the air space proximal to barn exhaust fans)
• Bodies of water with infected bird carcasses
• Close contact with (within 3 feet of) confirmed
  human cases
•  

15
Local Customs - Unique Exposures 

• Cock fighting
• Swan defeathering
• Playing with dead chickens
• Duck blood pudding, local customs
• Hunting practices

16
Alex

• Question
• Do you think Alex could have been exposed to
  highly pathogenic avian influenza A (H5N1) virus?

17
Using All of The Information
18
Alexs Situation

• 24 year old Alex sick for three days
• Fever
• Headache
• Cough
• Shortness of breath
• Muscle aches
• Watery diarrhea
• No one else sick
• Alex works on poultry farm where he handles
  poultry

19
Alex

• Question
• Would you suspect avian influenza A (H5N1) virus
  infection? Why or why not?

20
Part 1 Summary

• Individuals with avian influenza A (H5N1) virus
  infection may have non-specific lower respiratory
  symptoms, or (rarely) none at all
• Ask about recent exposure and contact with humans
  or animals that may have had avian influenza A
  (H5N1) virus infection

21
Case Management of Suspect Avian Influenza A
(H5N1) Virus Infection in Humans

• Part 2 Case Management of Suspected Human Cases
  of Avian Influenza A (H5N1) Virus Infection

22
Learning Objectives

• Testing available for diagnosing
• Clinical specimens
• Current treatment options
• Infection control measures

23
Part 2 Session Overview

• Laboratory Testing
• Treating Suspected Patients
• Infection Control in the Healthcare Setting

24
Laboratory Testing
25
Diagnostics

• Avian Influenza A (H5N1) Virus
• Specimens for testing
• Influenza A
• Imaging

26
Avian Influenza A (H5N1) VirusLaboratory Tests

• RT-PCR
• Detects viral RNA
• Diagnose H5N1 in humans
• BSL-2 conditions
• Results within hours
• Viral culture
• Only in enhanced BSL-3 laboratory
• Results in 2-10 days

• Serologic Testing
• Rise in H5N1 specific antibodies
• Testing only in enhanced BSL-3 laboratory

27
Clinical Specimens for Detecting Avian Influenza
A (H5N1)

• Lower Respiratory Tract
• Broncheoalveolar lavage fluid
• Endotracheal aspirate
• Pleural fluid
• Sputum
• Upper Respiratory Tract
• Oropharyngeal swabs
• Nasal Swab
• Collect multiple specimens from the same suspect
  H5N1 patient on different days for RT-PCR testing

Preferred specimens
28
Clinical Specimens for Testing

• Serology
• Acute and convalescent serum specimens
• Acute collected within 1 week of symptom onset
• Convalescent collected 2-4 weeks after symptom
  onset
• Other infections or concurrent illness
• Collect all possible specimens, serial collection

29
Clinical Specimens for Testing

• Autopsy Specimens
• Eight blocks or fixed-tissue specimens from each
  of the following sites
• Central (hilar) lung with segmental bronchi
• Right and left primary bronchi
• Trachea (proximal and distal)
• Pulmonary parenchyma from both right and left
  lung
• Major organs
• Myocardium (right and left ventricle)
• CNS (cerebral cortex, basal ganglia, pons,
  medulla, and cerebellum)
• Organ with significant gross or microscopic
  pathology)

30
Rapid Influenza Diagnostic Tests

• NOT RECOMMENDED TO DETECT AND DIAGNOSE H5N1 VIRUS
  INFECTION
• Many commercial kits available
• Results in 15-30 minutes
• Low sensitivity (FALSE NEGATIVES LIKELY)
• Positive result cannot differentiate seasonal
  influenza A from avian influenza A (H5N1) virus
  infection
• Negative result does not rule out avian influenza
  A (H5N1) virus infection as diagnosis

31
Laboratory Diagnostics

• CDCs influenza laboratory is nations influenza
  reference laboratory
• Capable of performing additional tests
• Immunohistochemical testing on autopsy specimens
• CDCs Emergency Response Hotline
• 770.488.7100

32
Imaging

• Chest X-ray changes of pneumonia are common in
  the lungs of H5N1 patients
• Non-specific changes
• Diffuse or patchy infiltrates
• Fluid in the space surrounding the lungs
• Cavities forming in the lung tissue

BBC News. http//bbb.co.uk Saturday, 3 December
2005
33
Avian Influenza A (H5N1) Virus Patients Chest
X-Rays
Day 5
Day 7
Day 10

• Chest x-ray of a patient with avian influenza A
  (H5N1) virus infection, shown by day of illness

Tran Tinh Hien, Nguyen Thanh Liem, Nguyen Thi
Dung, et al. New England Journal of Medicine. 18
March, 2004. vol. 350 no. 12. pp 1179-1188.
34
Treating Suspected Cases
35
Treatment Options

• Antivirals
• Supportive care

36
Neuraminidase Inhibitors

• Two drugs available
• Oseltamivir (Tamiflu) and Zanamivir
  (Relenza )
• Should be given as soon as possible
• Effective for treatment and prevention
• Used for seasonal influenza and infection with
  avian influenza A (H5N1) viruses

37
Oseltamivir

• Dosage for seasonal influenza
• Adults
• 75 mg twice a day for 5 days
• Children
• If for 5 days
• If 15 kg to twice a day for 5 days
• If 23 kg to twice a day for 5 days
• If 40 kg the dose should be 75 mg twice a day
  for 5 days

38
Oseltamivir

• Treatment for H5N1 patients
• Best dosage for H5N1 patients unknown
• Consider longer treatment (7 to 10 days) OR
• Higher doses (150 mg)
• Begin as soon as possible
• Dosage for prevention
• Once daily for 7 to 10 days after last exposure
• Side Effects
• Nausea and vomiting
• Skin rash
• Neurological problems

39
Oseltamivir

• Effectiveness in seasonal influenza
• Reduces influenza symptoms by 1 day
• Reduces some complications of influenza
• Cautions- Consider Risk versus Benefits
• People with kidney disease (adjust dose)
• Pregnant or nursing females
• Contraindication
• Hypersensitivity to any component of product
• Resistance
• Detected in some H5N1 patients

40
Zanamivir

• Inhaled by mouth via special device
• May be used for treatment of influenza 7 years
  of age
• Treatment dosage
• Once in morning and night, 5 days
• Side effects
• Wheezing, and breathing problems

41
Zanamivir

• Effectiveness in seasonal influenza
• Reduces influenza symptoms by one day
• Reduces lower respiratory tract complications
• Consider Risk vs. Benefit
• People with chronic respiratory disease
• Pregnant or nursing females
• Resistance
• Very rare in human cases of avian influenza A
  (H5N1) virus infections
• Active against Oseltamivir resistant H5N1 viruses

42
Other Treatments?

• Amantadine and Rimantadine
• Some H5N1 viruses are resistant
• Corticosteroids
• Not recommended
• Only for worsening sepsis with adrenal
  insufficiency

43
Treating Children

• Different Oseltamivir dosage
• Based on childs weight
• Not approved in children
• No aspirin for children
• Use Acetaminophen or Ibuprofen
• Children potentially infectious for longer
  periods than adults
• If child cannot remain hospitalized, educate
  family about infection control
• Source WHO Writing Group, Emerging Infectious
  Diseases, Vol. 12, No. 1, January 2006.

44
Antibiotics

• Broad-spectrum
• Do not use as a prophylactic
• Give empiric therapy for suspected bacterial
  pneumonia
• Secondary bacterial infection therapy
• Treat with intravenous antibiotics as recommended

45
Supportive Care

• Hospital care for suspected or confirmed avian
  influenza A (H5N1) cases should include
• Isolating the patient
• Supplemental oxygen and ventilation
• Intensive care support for organ failure

46
Infection Control in Health Care Setting
47
Infection Control Measures

• Patients hospitalized for clinical monitoring,
  diagnostic testing, and antiviral therapy
• Droplet/airborne precautions
• Isolation
• N95 respirators or more protective
• Eye protection (within 3 feet)
• Goggles or face shields

48
Infection Control Measures

• Standard Precautions
• Hand washing before and after contact with
  patient or potentially contaminated items
• Contact Precautions
• Gloves and gown worn
• Dedicated equipment used
• CDC recommendations http//www.cdc.gov/flu/avian/p
  rofessional/infect-control.htm

49
Managing Corpses

• No known risk of transmission from dead bodies
• Autopsy procedures could result in transmission
• Use appropriate protective equipment
• You should know
• Where corpses may be sent for disposal
• Cultural or religious beliefs to respect when
  handling corpses

50
Part 2 Summary

• Important appropriate clinical specimens are
  collected and tested
• Begin treatment with neuraminidase inhibitor
  (oseltamivir) immediately! Do not wait!

51
Case Management of Suspect Avian Influenza A
(H5N1) Virus Infection in Humans

• Part 3 Public Health Action

52
Learning Objectives

• Understand case management from public health
  perspective
• Recognize opportunities for public health
  authorities to effectively communicate avian
  influenza A (H5N1) information

53
Part 3 Session Overview

• Collect Case Information
• Classify case according to case definition for
  surveillance
• Facilitate specimen collection and laboratory
  testing
• Information on avian influenza A (H5N1) illness
• Infection control measures in the home
• Active case follow up
• Identify close contacts and recommend antiviral
  chemoprophylaxis (oseltamivir)
• Enhance surveillance

54
Pandemic Influenza Plan

• Know your role and responsibilities as outlined
  in your health departments plan
• Identify key collaborators before and during
  investigation

55
Collecting Case Information
56
Case Information

• Name of person reporting
• Healthcare facility name and location
• Patient information

• Name and contact Information
• Unique Identifier
• Occupation (address)
• Demographic
• Symptoms
• Test Results

• Treatment
• Outcome
• Travel history
• Potential exposures
• Close contacts

57
Updated Interim Guidance for Laboratory Testing
of Persons with Suspected Infection with Avian
Influenza A (H5N1) Virus in the United States

• Testing for avian influenza A (H5N1) virus
  infection is recommended for
• a patient who has an illness that
• requires hospitalization or is fatal AND
• has or had a documented temperature of 100.4
  F AND
• has radiographically confirmed pneumonia, acute
  respiratory distress syndrome (ARDS), or other
  severe respiratory illness for which an
  alternate diagnosis has not been established
  AND
• has at least one of the following potential
  exposures within 10 days of symptom onset

58
A) History of travel to a country with influenza
H5N1 documented in poultry, wild birds, and/or
humans, AND had at least one of the following
potential exposures during travel direct
contact with (e.g., touching) sick or dead
domestic poultry direct contact with surfaces
contaminated with poultry feces consumption
of raw or incompletely cooked poultry or poultry
products direct contact with sick or
dead wild birds suspected or confirmed to
have influenza H5N1 close contact (approach
within 1 meter approx. 3 feet) of a person
who was hospitalized or died due to a severe
unexplained respiratory illness
59
B) Close contact (approach within 1 meter
approx. 3 feet) of an ill patient who was
confirmed or suspected to have H5N1 or C)
Worked with live influenza H5N1 virus in a
laboratory.
60
Case by Case Considerations!

• Mild or atypical disease (hospitalized or
  ambulatory) with one of the exposures listed
  above
• Severe or fatal respiratory disease whose
  epidemiological information is uncertain,
  unavailable, or otherwise suspicious but does not
  meet the criteria above

61
Proposed Influenza Division/CDC Case Definitions

• Confirmed
• Suspect
• Report under investigation
• Non-case
• To be used for reporting purposes
• A separate CDC Health Alert Network was released
  that includes criteria for who should be tested
  for Influenza A (H5N1)

62
Proposed Influenza Division/CDC Case Definitions

• Confirmed Case (symptoms, exposure, laboratory
  confirmation)
• Documented temperature 38 C (100.4 F) and one
  of the following cough, sore throat, and/or
  respiratory distress
• AND
• One of the following exposures within 10 days of
  onset
• Direct exposure to sick or dead domestic poultry
• Direct exposure to surfaces contaminated with
  poultry feces
• Consumption of raw or partially cooked poultry or
  poultry products
• Close contact (within 3 feet) of an ill patient
  with confirmed or suspected avian influenza A
  (H5N1) infection
• Works with live HPAI (H5N1) virus in a laboratory
  
• AND

63
Proposed Influenza Division/CDC Case Definitions

• Confirmed Case (Continued)
• Positive for avian influenza A (H5N1) virus by
  one of the following methods
• Isolation of H5N1 from viral culture
• Positive RT-PCR for H5N1
• 4 fold rise in H5N1 specific antibody titer by
  microneutralization assay in paired sera
• Positive IFA for H5 antigen using H5N1 monoclonal
  antibodies

64
Proposed Influenza Division/CDC Case Definitions

• Suspect Case
• Documented temperature 38 C (100.4 F) and one
  of the following cough, sore throat, and/or
  respiratory distress AND
• One of the following exposures within 10 days of
  onset
• Direct exposure to sick or dead domestic poultry
• Direct exposure to surfaces contaminated with
  poultry feces
• Consumption of raw or partially cooked poultry or
  poultry products
• Close contact (within 3 feet) of an ill patient
  with confirmed or suspected avian influenza A
  (H5N1) virus infection
• Works with live HPAI (H5N1) virus in a laboratory
  
• Laboratory test for avian influenza A (H5N1) is
  pending, inadequate or unavailable

65
Proposed Influenza Division/CDC Case Definitions

• Report Under Investigation
• Additional information needed on clinical and
  exposure information
• Not a Case
• Negative avian influenza A (H5N1) virus testing
  result from a sensitive laboratory testing method
  using adequate and appropriately timed clinical
  specimens

66
Reporting

• Report through normal channels

• Information shared with WHOprobable and
  confirmed cases according to WHO case definition
• Help determine pandemic phase in US

Local PH
State PH
CDC
67
Facilitate Specimen Collection and Laboratory
Testing
68
Specimen Collection

• Best specimens
• Lower respiratory tract
• Broncheoalveolar lavage fluid
• Endotracheal aspirate
• Pleural fluid
• Upper respiratory tract
• Oropharyngeal swabs
• Have supplies stocked for timely collection of
  appropriate specimens

69
Laboratory Testing

• Be familiar with testing available in your area
• Know which laboratories can perform which tests
• Know tests available at CDC

70
Provide Information on Avian Influenza A (H5N1)
Illness
71
Avian Influenza A (H5N1) Virus Infection

• Emerging disease with evolving knowledge
• Empathy with public concerns
• Provide consistent and up to date literature to
  healthcare providers
• Appropriate reading level
• Translation for non-English speaking community
  members
• Information such as clinical features, exposure,
  and treatment options

72
Educate on Infection Control Measures in the Home
73
Infection Control Measures

• Give consistent and up to date literature to
  healthcare providers
• Hand washing
• Soap and water for 15-20 seconds
• Alcohol based sanitizer, 60 alcohol
• Limit close contact with patient
• CDC Guidance on Community Mask Use During a
  Pandemic. www.pandemicflu.gov

74
Infection Control Measures

• Seek medical care if condition worsens
• Stay home for 24 hours after symptoms resolve
• CDCs recommendation for in-home isolation
• http//www.cdc.gov/ncidod/sars/guidance/i/pdf/i.pd
  f

75
Conduct Active Case Follow Up
76
Active Follow Up

• Reasons for follow up
• Specimens for testing
• Timely notification of results
• Monitor delivery of antiviral therapy
• Secure antivirals if shortage
• Note unusual clinical presentations or
  complications
• Follow up by telephone
• Patient
• Healthcare provider (when available)
• Surrogate (e.g. spouse)

77
Identify Close Contacts
78
Definition of Close Contacts

• The definition of close contact is household and
  other contacts in work, school, and community
  settings who had close unprotected (i.e., not
  wearing PPE) contact in the 1 day before through
  14 days after the case patients symptom onset.
  Examples of close contact (within 1 meter) with a
  person include providing care, speaking with, or
  touching.
• http//www.who.int/csr/resources/publications/infl
  uenza/WHO_CDS_EPR_GIP_2006_4r1.pdf
• Depending on the specific circumstances suspect
  or confirmed cases that have completed isolation
  for at least 7 days, and who are no longer
  symptomatic, may not be considered a source of
  exposure to others.

79
Identifying Close Contacts

• List of contacts from patients case report form
• Close contact within 3 feet or 1 meter
• Sharing utensils, close conversation, direct
  contact
• Follow Up
• Characterize exposure
• Identify signs and symptoms
• Those with symptoms treated as potential case of
  infection with avian Influenza A (H5N1) virus

80
Recommendations to Contacts

• No symptoms
• Post-exposure prophylaxis for close contacts of a
  strongly suspected or confirmed human case of
  avian influenza A (H5N1) virus infection
• WHO high and moderate risk categories,
  poultry depopulators, and responders who have
  been on infected premises should receive post
  exposure prophylaxis

81
Instruction to Contacts

• No symptoms (continued)
• Self monitor for 10 days after last exposure
• Fever, respiratory symptoms, diarrhea, and/or
  conjunctivitis
• Seek medical care if symptoms present
• Notify public health authorities
• Follow infection control measures in the home

82
Enhance Surveillance
83
Enhance Surveillance during an Animal or Human
Outbreak of Avian Influenza A (H5N1) Virus
Infections

• Active case finding among occupationally exposed
• Sensitization of community to report illness
• Expand SARI and/or ILI surveillance to local
  hospitals, private practice etc...
• Screening in hospitals
• Training on procedures and reporting
• Door-to-door community surveillance
• Telephone hotlines for reporting

84
Part 3 Summary

• Public health authorities serve as protectors of
  their communitys health
• Important that public health authorities provide
  clear and consistent messages to patients and
  contacts
• Case management also means identifying contacts

85
Glossary

• Avian Influenza A Viruses
• Influenza A viruses that cause infection of wild
  birds and poultry.
• Contraindication
• A specific circumstance when the use of a certain
  treatment could be harmful.
• Seasonal Influenza
• Expected rise in influenza occurrence among
  humans living in temperate climates occurs
  during the winter season with strains of human
  influenza viruses that have minor changes from
  season to season.

86
References and Resources

• CDC Guidance for State and Local Health
  Departments for Conducting Investigations of
  Human Illness Associated with Domestic Highly
  pathogenic Avian Influenza Outbreaks in Animals
  (Draft).
• Preliminary clinical and epidemiological
  description of influenza A (H5N1) in Viet Nam. 12
  February 2004. http//www.who.int/csr/disease/avia
  n_influenza/guidelines/vietnamclinical/en/index.ht
  ml
• Tran Tinh Hien, et al. Avian Influenza A (H5N1)
  in 10 Patients in Vietnam. N Engl J Med March 18,
  2004 350(12), p 1179-1181.
• WHO interim guidelines on clinical management of
  humans infected by influenza A(H5N1), 2 March
  2004. http//www.who.int/csr/disease/avian_influen
  za/guidelines/clinicalmanage/en/index.html
• WHO pandemic influenza draft protocol for rapid
  response and containment. Updated draft 30 May
  2006. http//www.who.int/csr/disease/avian_influen
  za/guidelines/protocolfinal30_05_06a.pdf